Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human immunodeficiency virus type-1 (HIV-1) accessory gene vpr encodes a conserved 96-amino-acid protein that is necessary and sufficient for the HIV-1-induced block of cellular proliferation. Expression of vpr in CD4+ lymphocytes results in G2 arrest, followed by apoptosis. In a previous study, we identified the ataxia telangiectasia-mutated (ATM) and Rad3-related protein (ATR) as a cellular factor that mediates Vpr-induced cell cycle arrest. In the present study, we report that the breast cancer-associated protein-1 (BRCA1), a known target of ATR, is activated in the presence of Vpr. In addition, the gene encoding the growth arrest and DNA damage-45 protein alpha (GADD45alpha), a known transcriptional target of BRCA1, is upregulated by Vpr in an ATR-dependent manner. We demonstrate that RNAi-mediated silencing of either ATR or GADD45alpha leads to nearly complete suppression of the proapoptotic effect of Vpr. Our results support a model in which Vpr-induced apoptosis is mediated via ATR phosphorylation of BRCA1, and consequent upregulation of GADD45alpha.
 ...
PMID:ATR and GADD45alpha mediate HIV-1 Vpr-induced apoptosis. 1565 Jul 54

The protein transduction domain (PTD) from the HIV-1 TAT protein has been widely utilized to deliver biologically active macromolecules, including full-length proteins, into a variety of cell types in vitro and in vivo. Without additional targeting signals, the intracellular localization of the proteins delivered in this fashion appears to be cytoplasmic, nuclear or, as recently reported, endosomal. In this study, we show that the presence of the mitochondrial targeting signal (MTS) from hMnSOD on the N-terminus of TAT-fusion proteins directs them into mitochondria of breast cancer cells. We generated and purified fusion proteins containing GFP (MTS-GFP-TAT) or Exonuclease III (MTS-ExoIII-TAT) from Escherichia coli. The results of Western blots of subcellular fractions and fluorescent microscopic analyses revealed efficient protein transduction and mitochondrial localization of the fusion proteins. Specific exonuclease activity was found in the mitochondrial extracts isolated from MTS-ExoIII-TAT transduced cells. This increased exonuclease activity reduced the repair of mtDNA damage following oxidative stress. This diminished mtDNA repair led to a decrease in survival of breast cancer cells. Thus, the present study demonstrates the applicability of this new approach for intramitochondrial targeting of TAT-fusion proteins capable of modulating mitochondrial function and cell survival.
 ...
PMID:TAT-mediated protein transduction and targeted delivery of fusion proteins into mitochondria of breast cancer cells. 1572 31

QS-21A is one of the most promising new adjuvants for immune response potentiation and dose-sparing in vaccine therapy, given its exceedingly high level of potency and its favorable toxicity profile. Melanoma, breast cancer, small cell lung cancer, prostate cancer, HIV-1, and malaria are among the numerous maladies targeted in more than 80 recent and ongoing clinical trials involving QS-21A as a critical component for immune response augmentation in microgram doses. Herein is reported the first synthesis and structure verification of QS-21Aapi, applying novel glycosylation methodologies in the convergent modular construction of this rare and potent natural product immunostimulant.
 ...
PMID:Synthesis of the potent immunostimulatory adjuvant QS-21A. 1575 24

From the seeds of haricot beans (Phaseolus vulgaris), an antifungal peptide with a molecular mass around 7 kDa was purified by using a simple protocol consisting of affinity chromatography on Affi-gel blue gel and gel filtration on Superdex 75. This peptide named vulgarinin manifested an antifungal activity toward fungal species such as Fusarium oxysporum, Mycosphaerella arachidicola, Physalospora piricola and Botrytis cinerea, and an antibacterial action on Mycobacterium phlei, Bacillus megaterium, Bacillus subtilis and Proteus vulgaris. It also inhibited proliferation in leukemia cell lines L1210 and M1 and breast cancer cell line MCF-7. This peptide could reduce the activity of HIV-1 reverse transcriptase and inhibited translation in a cell-free rabbit reticulocyte lysate system. Its antifungal activity was retained after incubation with trypsin.
 ...
PMID:Vulgarinin, a broad-spectrum antifungal peptide from haricot beans (Phaseolus vulgaris). 1589 69

Stromal cell derived factor-1 (SDF-1), a CXC chemokine that play important roles in tumor growth, angiogenesis and metastasis of tumor cells, has a polymorphism at position 801 of its 3'-untranslated region, known as SDF1-3'A. This polymorphism has been investigated in HIV-1 infection and the susceptibility to breast cancer. In this investigation 72 lung cancer patients and 262 cases of normal healthy control were investigated for the genotype frequency of SDF-1 gene. Genotype frequency was carried out by PCR-RFLP method. Of 72 cancer patients 9 (12.5%) cases were emerged with AA genotype, 38 (52.8%) patients with AG and 25 (34.7%) with GG genotype. Comparison of these data with genotype frequency of SDF-1 gene of 262 normal healthy controls indicates a significant difference among patient and control groups (P=0.008). Results also showed that the frequency of AA and AG genotypes was higher among patients, while the frequency of GG genotype was lower compared to the controls. By considering the importance of SDF-1 in several physiological processes and also its significant biological behavior in cancer metastasis and on the basis of the results of this study we conclude that AA and AG genotypes of SDF-1 may be considered as factors increasing the susceptibility of Iranian patients to lung cancer.
 ...
PMID:Stromal cell-derived factor-1 (SDF-1) gene and susceptibility of Iranian patients with lung cancer. 1595 92

Nasopharyngeal carcinoma (NPC) is a tumor derived from epithelial cells and Epstein-Barr virus infection has been reported to be a cause of this disease. Chemokine receptor CXCR4 was found to be involved in HIV infection and was highly expressed in human malignant breast tumors and the ligand for CXCR4, CXCL12 (SDF-1), exhibited high expression in organs in which breast cancer metastases are often found. The metastatic pattern of NPC is quite similar to that of malignant breast tumors. In this study, we investigated the expression of CXCR4 in nasopharyngeal carcinoma (NPC) tissues by immunohistostaining. We found different staining patterns, which included localization in the nucleus, membrane, cytoplasm or a combination of them. The staining intensity was also variable among samples. The metastatic rates in patients with high compared to low or absent expression was 38.6% versus 19.8%, respectively (P = 0.004). High expression of CXCR4 was associated with poor overall survival (OS = 67.05% versus 82.08%, P = 0.0225). These results suggest that CXCR4 may be involved in the progression of NPC and that a high level of CXCR4 expression could be used as a prognostic factor.
 ...
PMID:Expression of chemokine receptor CXCR4 in nasopharyngeal carcinoma: pattern of expression and correlation with clinical outcome. 1597 37

Stromal cell-Derived Factor-1 (SDF-1, CXCL12) is one the ELR- CXC angiogenic chemokines. It contributes to hematopoiesis and lymphocyte trafficking. SDF-1 and its exclusive receptor, CXCR4, are reported to play important roles in tumor growth, angiogenesis and metastasis of different types of tumors such as breast, lung, prostate and pancreatic cancers. SDF-1 gene polymorphism, known as SDF1-3'A, has been investigated in HIV-1 infection and the incidence of breast cancer. This investigation was aimed to study the frequency of SDF1-3'A mutation in Iranian women with breast cancer. Results showed that the frequency of AA and AG genotypes was higher among patients, while the frequency of GG genotype was lower compared to the controls. Thus AA and AG genotypes of SDF-1 may be considered as factors increasing the susceptibility of Iranian women to breast cancer.
 ...
PMID:Stromal cell-derived factor-1 (SDF-1) alleles and susceptibility to breast carcinoma. 1597 29

The recently reported FACS-based CD107 assay has been used in human HIV and CMV antigen models as well as in the ex vivo analysis of tumor cytolytic T cells in a melanoma model by a single group. The purpose of our study was to validate this assay and to use it in previously untested viral and tumor antigen models. Specifically, we investigated the use of the novel CD107 cytotoxicity assay in the detection of influenza and HER2/neu tumor-specific cytolytic CD8+ T cells. CD8+ T cells from HLA-A2+ healthy donors were stimulated with autologous dendritic cells pulsed with FluM or the HER2/neu peptides, E75 or GP2. These CD8+ T cells were then tested in cytotoxicity assays at varying effector:target (E:T) ratios against T2 targets. Cytotoxicity was measured by detection of CD107a and b on the surface of CD8+ T cells. An E:T of 1:5 was found to optimize the resulting percentage of CD8+CD107+ T cells. E75- and GP2-stimulated CD8+ T cells were then tested in cytotoxicity assays with MCF-7 (HER2/neu+HLA-A2+) and AU565 (HER2/neu+HLA-A2-) tumor cells. Cytotoxicity was measured by both the CD107 assay and the (51)Cr release assay. Results of cytotoxicity were then correlated between these two assays. In representative experiments, the CD107 assay identified average specific increases for E75- and GP2-stimulated cells of 4.26 and 3.57%, respectively. These results correlated favorably with cytotoxicity as measured by the traditional (51)Cr assay. These findings confirm preliminary reports of the CD107 assay and suggest its usefulness for monitoring cancer trials.
Breast Cancer Res Treat 2005 Jul
PMID:Evaluation of the CD107 cytotoxicity assay for the detection of cytolytic CD8+ cells recognizing HER2/neu vaccine peptides. 1598 Sep 96

In this article the positive effects of massage therapy on biochemistry are reviewed including decreased levels of cortisol and increased levels of serotonin and dopamine. The research reviewed includes studies on depression (including sex abuse and eating disorder studies), pain syndrome studies, research on auto-immune conditions (including asthma and chronic fatigue), immune studies (including HIV and breast cancer), and studies on the reduction of stress on the job, the stress of aging, and pregnancy stress. In studies in which cortisol was assayed either in saliva or in urine, significant decreases were noted in cortisol levels (averaging decreases 31%). In studies in which the activating neurotransmitters (serotonin and dopamine) were assayed in urine, an average increase of 28% was noted for serotonin and an average increase of 31% was noted for dopamine. These studies combined suggest the stress-alleviating effects (decreased cortisol) and the activating effects (increased serotonin and dopamine) of massage therapy on a variety of medical conditions and stressful experiences.
 ...
PMID:Cortisol decreases and serotonin and dopamine increase following massage therapy. 1616 47

Chronic illness is disruptive, threatening people's sense of identity and taken for granted assumptions. Transformations in values, expectations and life priorities are likely to be experienced and in order to regain a coherent sense of self, people must interpret their experiences. People with difficult to diagnose illnesses can find themselves living with greater uncertainty and stigma. This paper explores how people with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) describe and interpret their illness experience by applying Arthur Frank's narrative typologies to analyse interviews with 17 British people with CFS/ME. The analysis proposes that a trajectory of narrative typologies is experienced, starting with a restitution narrative, moving to a chaos narrative and, for most, back to a restitution narrative and on to a quest narrative. The presentation of narrative types put forward by people living with CFS/ME differ to those presented by people who are HIV positive and have been treated for breast cancer.
 ...
PMID:Quest, chaos and restitution: living with chronic fatigue syndrome/myalgic encephalomyelitis. 1623 13


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>